Pharmacological characterisation of the dopamine-sensitive adenylate cyclase in cockroach brain: evidence for a distinct dopamine receptor

Life Sci. 1987 Dec 21;41(25):2705-15. doi: 10.1016/0024-3205(87)90463-2.

Abstract

Dopamine increases cyclic AMP production in crude membrane preparations of cockroach brain with plateaus in cyclic AMP production occurring between 1-10 microM and at 10 mM. Maximal production of cyclic AMP is 2.25 fold greater than that of control values. Octopamine also increases cyclic AMP production with a Ka of 1.4 microM and maximal production 3.5 fold greater than that of control. 5-Hydroxytryptamine does not increase cyclic AMP production. The effects of octopamine and dopamine are fully additive. The vertebrate dopamine agonists ADTN and epinine stimulate the dopamine-sensitive adenylate cyclase (AC) with Ka values of 4.5 and 0.6 microM respectively and with maximal effectiveness 1.7 fold greater than that of control. The selective D2-dopamine agonist LY-171555 stimulates cyclic AMP production to a similar extent with a Ka of 50 microM. Other dopamine agonists (apomorphine, SKF-82526, SKF-38393) have no stimulatory effects. The octopamine-sensitive AC is inhibited by a variety of antagonists known to affect octopamine and dopamine receptors, with the following order of potency: mianserin greater than phentolamine greater than cyproheptadine greater than piflutixol greater than cis-flupentixol greater than SCH-23390 greater than (+)-butaclamol greater than SKF-83566 greater than SCH-23388 greater than sulpiride greater than spiperone greater than haloperidol. The dopamine-sensitive AC is inhibited by the same compounds with the following order of potency: piflutixol greater than cis-flupentixol greater than (+)-butaclamol greater than spiperone greater than or equal to SCH-23390 greater than cyproheptadine greater than SKF-83566 greater than SCH 23388 greater than mianserin greater than phentolamine greater than sulpiride greater than haloperidol. With the exception of mianserin, 3H-piflutixol is displaced from brain membranes by dopamine antagonists with an order of potency similar to that observed for the inhibition of dopamine-sensitive AC. The results indicate that the octopamine- and dopamine-sensitive AC in cockroach brain can be distinguished pharmacologically and the dopamine receptors coupled to AC have pharmacological characteristics distinct from vertebrate D1- and D2-dopamine receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Animals
  • Antipsychotic Agents / pharmacology
  • Brain / drug effects
  • Brain / enzymology*
  • Cockroaches
  • Cyclic AMP / biosynthesis
  • Dopamine / pharmacology*
  • Kinetics
  • Male
  • Octopamine / pharmacology
  • Receptors, Dopamine / metabolism*
  • Serotonin / pharmacology

Substances

  • Antipsychotic Agents
  • Receptors, Dopamine
  • Octopamine
  • Serotonin
  • 2-octopamine
  • Cyclic AMP
  • Adenylyl Cyclases
  • Dopamine